Intraspecific hybrid cell strains are being used to study the inheritance of mitochondrial DNA and its interactions with nuclear DNA. We have previously obtained evidence for intraspecific recombination in mt-DNA by physical means; we are now attempting to extend this study using genetic markers such as antibiotic resistance. We have found that "cytoplasts" prepared by cytochalazin B enucleation of ouabain resistant cells may be fused with ouabain sensitive cells and provide sufficient ouabain resistance to allow a selective providing workable enrichment for cells which have received a cytoplast. In other projects, our new found ability to influence at will the direction of chromosome loss in intraspecific hybrid cell strains is being used in a variety of experiments in which cells which do not divide in culture are being hybridized with cells which do: e.g., neurons and cardiac muscle cells fused to fibroblasts. In collaboration with other groups at NIH these studies are being extended to haematopoetic cells. The different electrophoretically separable forms of thymidine kinase are being studied in hybrid cells selected in HAT medium and we are extending these studies to include the various complementation groups of xeroderma pigmentosum. We are studying the growth of normal, differentiated thyroid cells and their hybrid derivatives in an attempt to produce easily modifiable genetic strains suitable for studies of control of thyroid specific functions. We are pursuing in situ hybridization to attempt to map the chromosomal loci which hybridize with the messenger RNA preps (made by immune precipitation) which synthesize the heavy chain of immunoglobulin. These mRNA preparations are also used as probes to locate specific gene sequences in DNA extracted from hybrid cells, differentiated cells and their subcellular fractions. Finally, we have made a PL/1 program which accomplishes reverse translations from known aminoacid sequences and which checks these for providing maximum and minimum opportunity for secondary structure codings in the mRNA or DNA. We are especially interested in the Wu-Kabat hypervariable regions of immunoglobulin.